1300 Cardiovascular Drugs Pharmacopoeias. In Jpn and US. Uses and Administration dine, but authorities have differed as to whether the drug should USP 31 ( Acetate). A white or almost white powder is an antihypertensive with actions and uses similar to be stopped before elective surgery. Former US licensed product with not more than a slight odour. Sparingly soluble in water and those of (below). After oral administration, gua- information recommended stopping up to 2 or 3 weeks before- in 0.1N hydrochloric acid; soluble in alcohol and in propylene nadrel acts within 2 hours with the maximum effect after 4 to 6 hand. In patients undergoing emergency procedures or where glycol. A 0.7% solution in water has a pH of 5.5 to 7.0. Store in hours. The hypotensive effect is reported to last for 4 to 14 hours treatment has not been interrupted large doses of atropine should airtight containers. Protect from light. following a single dose. It has been given orally as the in be given before induction of anaesthesia. the management of , although it has largely been su- Patients undergoing treatment with eye drops containing Adverse Effects and Precautions perseded by other drugs less likely to cause orthostatic hypoten- As for Hydrochloride, p.1247. guanethidine should be examined regularly for signs of conjunc- sion. tival damage. Overdosage. Overdosage with guanabenz has been reported.1 Preparations The main symptoms were lethargy, drowsiness, bradycardia, and Interactions hypotension. A 45-year-old woman who had taken 200 to USP 31: Guanadrel Sulfate Tablets. Patients taking guanethidine may show increased sensitivity to 240 mg of guanabenz with alcohol recovered after gastric lavage the action of , amfetamine, and other sympathomimet- and intravenous fluids; a 3-year-old child who had taken 12 mg ics, resulting in exaggerated pressor effects. The hypotensive ef- fects may also be antagonised by tricyclic , of guanabenz responded to atropine and . Naloxone Guanethidine Monosulfate (USAN, rINNM) had little effect in either patient. MAOIs, and derivatives and related antipsychot- Guanéthidine, monosulfate de; Guanethidine Monosulphate ics (although may also exacerbate orthostatic hy- 1. Hall AH, et al. Guanabenz overdose. Ann Intern Med 1985; 102: (BANM); Guanethidini Monosufas; Guanethidini monosulfas; potension, which may be more relevant clinically). In the UK 787–8. Guanethidini Sulfas; Guanethidin-monosulfát; Guanetidiinimono- licensed product information suggests that MAOIs should be Interactions sulfaatti; Guanetidinmonosulfat; Guanetidin-monoszulfát; Guane- stopped at least 14 days before beginning guanethidine, although As for Clonidine Hydrochloride, p.1248. tidino monosulfatas; Monosulfato de guanetidina; NSC-29863 in the USA a minimum of a week has been recommended as ad- Pharmacokinetics (guanethidine hemisulfate); Su-5864 (guanethidine hemisulfate). equate. It has been reported that oral contraceptives may reduce About 75% of an oral dose of guanabenz is absorbed and under- 1-[2-(Perhydroazocin-1-yl)ethyl] monosulfate. the hypotensive action of guanethidine. Use of digoxin or other goes extensive first-pass metabolism. Peak plasma concentra- digitalis derivatives with guanethidine may cause excessive Гуанетидина Моносульфат bradycardia. tions occur about 2 to 5 hours after a dose. It is about 90% bound C H N ,H SO = 296.4. to plasma proteins. Guanabenz is mainly excreted in urine, al- 10 22 4 2 4 The hypotensive effects of guanethidine may be enhanced by thi- CAS — 55-65-2 (guanethidine); 60-02-6 (guanethidine azide diuretics, other antihypertensives, and levodopa. Alcohol most entirely as metabolites, with less than 1% as unchanged hemisulfate); 645-43-2 (guanethidine monosulfate). may cause orthostatic hypotension in patients taking guanethi- drug; about 10 to 30% is excreted in faeces. The average elimi- ATC — C02CC02; S01EX01. dine. nation half-life is reported to range from 4 to 14 hours. ATC Vet — QC02CC02; QS01EX01. Uses and Administration Pharmacokinetics Guanethidine is variably and incompletely absorbed from the Guanabenz is an alpha2-adrenoceptor agonist with actions and uses similar to those of clonidine (p.1248). It is used in the man- H gastrointestinal tract with less than 50% of the dose reaching the N NH2 systemic circulation. It is actively taken up into neu- agement of hypertension (p.1171), either alone or with other N antihypertensives, particularly diuretics. rones by the mechanism responsible for noradrenaline reuptake. A plasma concentration of 8 nanograms/mL is reported to be Guanabenz is given orally as the acetate, but doses are usually NH necessary for adrenergic blockade, but the dose required to expressed in terms of the base. Guanabenz acetate 5 mg is equiv- achieve this varies between individuals due to differences in ab- alent to about 4 mg of guanabenz. (guanethidine) sorption and metabolism. Guanethidine is partially metabolised In hypertension, the usual dose is 4 mg twice daily initially; the in the liver, and is excreted in the urine as metabolites and daily dose may be increased by amounts of 4 to 8 mg every 1 to Pharmacopoeias. In Eur. (see p.vii), Jpn, and US. unchanged guanethidine. It has a terminal half-life of about 5 2 weeks according to response. Doses of up to 32 mg twice daily Chin. includes the hemisulfate. days. Guanethidine does not penetrate the blood-brain barrier have been used. Ph. Eur. 6.2 (Guanethidine Monosulphate). A colourless crys- significantly. Preparations talline powder. Freely soluble in water; practically insoluble in Uses and Administration USP 31: Guanabenz Acetate Tablets. alcohol. A 2% solution in water has a pH of 4.7 to 5.5. Protect Guanethidine is an antihypertensive that acts by selectively in- from light. Proprietary Preparations (details are given in Part 3) hibiting transmission in postganglionic adrenergic nerves. It is USP 31 (Guanethidine Monosulfate). A white to off-white crys- Braz.: Lisapres; USA: Wytensin. believed to act mainly by preventing the release of noradrenaline talline powder. Very soluble in water; sparingly soluble in alco- at nerve endings. Guanethidine causes the depletion of noradren- hol; practically insoluble in chloroform. A 2% solution in water aline stores in peripheral sympathetic nerve terminals but does has a pH of 4.7 to 5.7. not prevent the secretion of by the adrenal me- Guanadrel Sulfate (USAN, rINNM) Adverse Effects dulla. CL-1388R; Guanadrel, Sulfate de; Guanadrel Sulphate; Gua- The commonest adverse effects of guanethidine are severe pos- When given orally its maximal effects may take 1 to 3 weeks to nadreli Sulfas; Sulfato de guanadrel; U-28288D. 1-(Cyclohexane- tural and exertional hypotension and diarrhoea which may be appear on continued dosing and persist for 1 to 3 weeks after spiro-2′-[1′,3′]dioxolan-4′-ylmethyl)guanidine sulfate; 1-(1,4-Di- particularly troublesome during the initial stages of therapy and treatment has been stopped. It causes an initial reduction in car- oxaspiro[4.5]dec-2-ylmethyl)guanidine sulfate. during dose adjustment. Dizziness, syncope, muscle weakness, diac output but its main hypotensive effect is to cause peripheral and lassitude are liable to occur, especially on rising from sitting vasodilatation; it reduces the which normally Гуанадрела Сульфат or lying. Orthostatic hypotension may be severe enough to pro- results from standing up and which is the result of reflex sympa- (C10H19N3O2)2,H2SO4 = 524.6. voke angina, renal impairment, and transient cerebral ischaemia. thetic nervous activity. In the majority of patients it reduces CAS — 40580-59-4 (guanadrel); 22195-34-2 (guanadrel Other frequent adverse effects are bradycardia, failure of ejacu- standing blood pressure but has a lesser effect on supine blood sulfate). lation, fatigue, headache, and salt and water retention and oede- pressure. When applied topically to the eye guanethidine reduces ma, which may be accompanied by breathlessness and may oc- the production of aqueous humour. casionally precipitate overt heart failure. Guanethidine is used in the management of hypertension NH Nausea, vomiting, dry mouth, nasal congestion, parotid tender- (p.1171). Eye drops of guanethidine have been used for open- ness, blurring of vision, depression, myalgia, muscle tremor, par- angle glaucoma (p.1873) and for lid retraction associated with O aesthesias, hair loss, dermatitis, disturbed micturition, priapism, hyperthyroidism. Guanethidine has also been used in the man- N NH2 H2SO4 aggravation or precipitation of asthma, and exacerbation of pep- agement of neuropathic pain syndromes (see below). H tic ulcer disease have also been reported. Guanethidine may pos- Guanethidine is used in the treatment of hypertension when other O sibly cause anaemia, leucopenia, and thrombocytopenia. 2 drugs have proved inadequate, but it has largely been superseded When guanethidine is used as eye drops, common adverse ef- by other drugs less likely to cause orthostatic hypotension. Tol- fects are conjunctival hyperaemia and miosis. Burning sensa- erance to guanethidine has occurred in some patients; this may Pharmacopoeias. In US. tions and ptosis have also occurred. Superficial punctate keratitis be countered by concomitant diuretic therapy. USP 31 (Guanadrel Sulfate). A white to off-white crystalline has been reported particularly after prolonged use of high doses. In hypertension, the usual initial oral dose of guanethidine mono- powder. Soluble in water; slightly soluble in alcohol and in sulfate has been 10 mg daily. This is increased by increments of acetone; sparingly soluble in methyl alcohol. Treatment of Adverse Effects Withdrawal of guanethidine or dose reduction reverses many ad- 10 to 12.5 mg, not more often than every 5 to 7 days, according to Adverse Effects, Treatment, and Precautions verse effects. Diarrhoea may also be controlled by giving co- response. The usual maintenance dose has been 25 to 50 mg once As for Guanethidine Monosulfate, below. Guanadrel has been deine phosphate or antimuscarinics. If overdosage occurs the daily. reported to cause less diarrhoea, and less orthostatic hypotension benefit of gastric decontamination is uncertain, but activated Children have been given 200 micrograms/kg daily with incre- on rising in the morning, than guanethidine, but orthostatic charcoal may be given if the patient presents within 1 hour. Hy- ments of 200 micrograms/kg every 7 to 10 days until a satisfac- symptoms seem to occur with a similar frequency to guanethi- potension may respond to placing the patient in the supine posi- tory response is achieved. dine during the day. tion with the feet raised. If hypotension is severe it may be nec- Guanethidine monosulfate has been given intramuscularly in the Interactions essary to give intravenous fluid replacement and small doses of treatment of hypertensive crises, including severe pre-eclampsia, As for Guanethidine Monosulfate, below. vasopressors may be given cautiously. The patient must be mon- but more suitable drugs are available. An intramuscular dose of itored for several days. 10 to 20 mg is reported to produce a fall in blood pressure within Pharmacokinetics 30 minutes. Guanadrel is rapidly and almost completely absorbed from the Precautions Eye drops containing guanethidine monosulfate have been used gastrointestinal tract, with a bioavailability of about 85%. It is Guanethidine should not be given to patients with phaeochromo- in the treatment of open-angle glaucoma (usually combined widely distributed throughout the body and about 20% is bound cytoma, as it may cause a hypertensive crisis, or to patients with with adrenaline), and for the lid retraction that may accompany to plasma proteins. It is reported not to cross the blood-brain bar- heart failure not caused by hypertension. hyperthyroidism. rier. Plasma concentrations decline in a biphasic manner: the It should be used with caution in patients with renal impairment, half-life varies widely between individuals, in the initial phase cerebrovascular disorders, or ischaemic heart disease, or with a Pain syndromes. Sympathetic nerve blocks may be used in the from 1 to 4 hours, and in the terminal phase from 5 to 45 hours, history of peptic ulcer disease or asthma. Exercise and heat may management of acute or chronic pain associated with a well-de- with a mean of about 10 hours. Guanadrel is metabolised in the increase the hypotensive effect of guanethidine, and dosage re- fined anatomical site. Guanethidine is one of a number of drugs liver and about 85% is excreted in the urine over 24 hours as the quirements may be reduced in patients who develop fever. that have been used for intravenous regional sympathetic block unchanged drug and its metabolites. About 40 to 50% of the drug There may be an increased risk of cardiovascular collapse or car- in the management of neuropathic pain (see Complex Regional is excreted unchanged. diac arrest in patients undergoing surgery while taking guanethi- Pain Syndrome, p.6), to reduce pain and to maintain blood flow. Guanadrel Sulfate/Heparin 1301 However, reviews and studies1,2 in patients with reflex sympa- tension the usual initial dose is 1 mg daily increasing after 3 to 4 odarone hydrochloride, ampicillin sodium, aprotinin, benzylpen- thetic dystrophy failed to find any benefit from guanethidine. weeks to 2 mg daily if necessary. icillin potassium or sodium, cefalotin sodium, ciprofloxacin lac- 1. Jadad AR, et al. Intravenous regional sympathetic blockade for ◊ Reviews. tate, cytarabine, dacarbazine, daunorubicin hydrochloride, pain relief in reflex sympathetic dystrophy: a systematic review diazepam, hydrochloride, doxorubicin hydrochlo- and a randomized, double-blind crossover study. J Pain Symp- 1. Cornish LA. hydrochloride: a centrally acting anti- hypertensive agent. Clin Pharm 1988; 7: 187–97. ride, droperidol, erythromycin lactobionate, gentamicin sulfate, tom Manage 1995; 10: 13–20. lactate, hyaluronidase, hydrocortisone sodium succi- 2. Livingstone JA, Atkins RM. Intravenous regional guanethidine Tourette’s syndrome. Guanfacine may be used as an alterna- nate, kanamycin sulfate, meticillin sodium, netilmicin sulfate, blockade in the treatment of post-traumatic complex regional tive to clonidine in the management of patients with mild to mod- some analgesics, oxytetracycline hydrochloride, some pain syndrome type 1 (algodystrophy) of the hand. J Bone Joint erate symptoms of Tourette’s syndrome (see Tics, p.954). First- Surg Br 2002; 84: 380–6. phenothiazines, polymyxin B sulfate, streptomycin sulfate, tetra- line use of these drugs is increasingly favoured in such patients cycline hydrochloride, tobramycin sulfate, vancomycin hydro- Preparations because of a relative lack of serious adverse effects when com- chloride, and vinblastine sulfate. Heparin sodium has also been BP 2008: Guanethidine Tablets; pared with the commonly used . reported to be incompatible with cisatracurium besilate,1 labeta- USP 31: Guanethidine Monosulfate Tablets. Preparations lol hydrochloride,2 levofloxacin,3 nicardipine hydrochloride,4 re- 5 6 Proprietary Preparations (details are given in Part 3) USP 31: Guanfacine Tablets. teplase, and vinorelbine tartrate. Although visually compati- 7 Austral.: Ismelin; Gr.: Ismelin; UK: Ismelin; USA: Ismelin†. Proprietary Preparations (details are given in Part 3) ble, cefmetazole sodium is reported to inactivate heparin Multi-ingredient: Arg.: Normatensil†; Austria: Thilodigon†; Ger.: Es- Belg.: Estulic; Cz.: Estulic†; Fr.: Estulic; Hung.: Estulic; Jpn: Estulic†; Neth.: sodium. imil†; Thilodigon; Irl.: Ganda; USA: Esimil. Estulic†; Rus.: Estulic (Эстулик); USA: Tenex. Glucose can have variable effects,8,9 but glucose-containing solutions are generally considered suitable diluents for heparin. Incompatibility has also been reported between heparin and fat Guanfacine Hydrochloride (BANM, USAN, rINNM) emulsion. Heparin (BAN) 1. Trissel LA, et al. Compatibility of cisatracurium besylate with BS-100-141; Guanfacine, Chlorhydrate de; Guanfacini Hydro- Hepariini; Heparina; Heparinum; Heparyna. selected drugs during simulated Y-site administration. Am J chloridum; Hidrocloruro de guanfacina; LON-798. N-Amidino- Health-Syst Pharm 1997; 54: 1735–41. CAS — 9005-49-6. 2-(2,6-dichlorophenyl)acetamide hydrochloride. 2. Yamashita SK, et al. Compatibility of selected critical care drugs ATC — B01AB01; C05BA03; S01XA14. during simulated Y-site administration. Am J Health-Syst Pharm Гуанфацина Гидрохлорид ATC Vet — QB01AB01; QC05BA03; QS01XA14. 1996; 53: 1048–51. C9H9Cl2N3O,HCl = 282.6. 3. Saltsman CL, et al. Compatibility of levofloxacin with 34 medi- Description. Heparin is an anionic polysaccharide of mamma- cations during simulated Y-site administration. Am J Health-Syst CAS — 29110-47-2 (guanfacine); 29110-48-3 (guanfa- lian origin with irregular sequence. It consists principally of al- cine hydrochloride). Pharm 1999; 56: 1458–9. ternating iduronate and glucosamine residues, most of which are 4. Chiu MF, Schwartz ML. Visual compatibility of injectable drugs ATC — C02AC02. sulfated. It may be described as a sulfated glucosaminoglycan. used in the intensive care unit. Am J Health-Syst Pharm 1997; ATC Vet — QC02AC02. Heparin has the characteristic property of delaying the clotting of 54: 64–5. freshly shed blood. It may be prepared from the lungs of oxen or 5. Committee on Safety of Medicines/Medicines Control Agency. the intestinal mucosa of oxen, pigs, or sheep. Reteplase (Rapilysin): incompatibility with heparin. Current Heparin is often described in the literature as standard heparin or Problems 2000; 26: 5. Also available at: Cl http://www.mhra.gov.uk/home/idcplg?IdcService=GET_ O NH unfractionated heparin to distinguish it from low-molecular- FILE&dDocName=CON007462&RevisionSelectionMethod= weight heparins. LatestReleased (accessed 23/06/06) N NH 6. Balthasar JP. Concentration-dependent incompatibility of vinor- 2 elbine tartrate and heparin sodium. Am J Health-Syst Pharm H Heparin Calcium (BANM) Cl 1999; 56: 1891. Calcium Heparin; Hepariinikalsium; Heparin Kalsiyum; Heparin 7. Hutching SR, et al. Compatibility of cefmetazole sodium with Sodyum; Heparin vápenatá sůl; Heparina cálcica; Héparine cal- (guanfacine) commonly used drugs during Y-site delivery. Am J Health-Syst cique; Heparinkalcium; Heparino kalcio druska; Heparinum calci- Pharm 1996; 53: 2185–8. cum; Heparyna wapniowa. 8. Anderson W, Harthill JE. The anticoagulant activity of heparins in dextrose solutions. J Pharm Pharmacol 1982; 34: 90–6. Pharmacopoeias. In US. CAS — 37270-89-6. USP 31 (Guanfacine Hydrochloride). Store in airtight contain- 9. Wright A, Hecker J. Long term stability of heparin in dextrose- ATC — B01AB01; C05BA03; S01XA14. saline intravenous fluids. Int J Pharm Pract 1995; 3: 253–5. ers. Protect from light. ATC Vet — QB01AB01; QC05BA03; QS01XA14. Adverse Effects and Precautions Pharmacopoeias. In Eur. (see p.vii), Int., and US. Units As for Clonidine Hydrochloride, p.1247. Rebound hypertension Ph. Eur. 6.2 (Heparin Calcium). The potency of heparin calcium may occur but is delayed due to the longer half-life. intended for parenteral use is not less than 150 international units The fifth International Standard for unfractionated per mg and the potency of heparin calcium not intended for heparin was established in 1998. The USP 31 states ◊ Reviews. parenteral use is not less than 120 international units per mg, both that USP and international units are not equivalent, al- 1. Jerie P. Clinical experience with guanfacine in long-term treat- calculated with reference to the dried substance. A white or al- ment of hypertension, part II: adverse reactions to guanfacine. Br though doses expressed in either appear to be essential- J Clin Pharmacol 1980; 10 (suppl 1): 157S–164S. most white, hygroscopic powder. Freely soluble in water. A 1% ly the same. 2. Board AW, et al. A postmarketing evaluation of guanfacine hy- solution in water has a pH of 5.5 to 8.0. Store in airtight contain- drochloride in mild to moderate hypertension. Clin Ther 1988; ers. 10: 761–75. USP 31 (Heparin Calcium). The calcium salt of heparin with a Adverse Effects Heparin can give rise to haemorrhage as a consequence Withdrawal. Rapid reduction of the guanfacine dosage result- potency, calculated on the dried basis, of not less than 140 USP ed in rebound hypertension leading to generalised seizures and units in each mg. USP heparin units are not equivalent to inter- of its action. It can also cause thrombocytopenia, either coma in a 47-year-old patient with renal failure who was receiv- national units. The source of the material is usually the intestinal through a direct effect or through an immune effect ing haemodialysis.1 Use with phenobarbital may have enhanced mucosa or other suitable tissues of domestic mammals used for producing a platelet-aggregating antibody. Consequent the metabolism of guanfacine and contributed to the develop- food by man and should be stated on the label. A 1% solution in water has a pH of 5.0 to 7.5. Store in airtight containers at tem- platelet aggregation and thrombosis may therefore ex- ment of the withdrawal effect. acerbate the condition being treated. The incidence of 1. Kiechel JR, et al. Pharmacokinetic aspects of guanfacine with- peratures below 40°, preferably between 15 and 30°. drawal syndrome in a hypertensive patient with chronic renal Incompatibility. See Heparin Sodium, below. thrombocytopenia is reported to be greater with bovine failure. Eur J Clin Pharmacol 1983; 25: 463–6. than porcine heparin. Interactions Heparin Sodium (BANM, rINN) Hypersensitivity reactions may occur, as may local As for Clonidine Hydrochloride, p.1248. Hepariininatrium; Heparin sodná sůl; Heparina sódica; Héparine irritant effects, and skin necrosis. Alopecia and osteo- Pharmacokinetics sodique; Heparinnatrium; Heparino natrio druska; Heparinum porosis resulting in spontaneous fractures have oc- Guanfacine is rapidly absorbed after oral doses and peak plasma natricum; Heparyna sodowa; Sodium Heparin; Soluble Heparin. curred after prolonged use of heparin. concentrations occur 1 to 4 hours after ingestion. The oral bioa- Гепарин Натрий vailability is reported to be about 80%. It is about 70% bound to Effects on the adrenal glands. Heparin inhibits the secretion CAS — 9041-08-1. 1 plasma proteins. It is excreted in urine as unchanged drug and ATC — B01AB01; C05BA03; S01XA14. of aldosterone and so may cause hyperkalaemia. Although all metabolites; about 50% of a dose is reported to be eliminated ATC Vet — QB01AB01; QC05BA03; QS01XA14. patients treated with heparin may develop reduced aldosterone unchanged. The normal elimination half-life ranges from 10 to concentrations, most are able to compensate through the renin- Pharmacopoeias. In Chin., Eur. (see p.vii), Int., Jpn, and US. angiotensin system. Patients on prolonged heparin therapy or 30 hours, tending towards the upper range in older patients. Ph. Eur. 6.2 (Heparin Sodium). The potency of heparin sodium 1 those unable to compensate, such as patients with diabetes mel- Renal impairment. A study in patients with normal or im- intended for parenteral use is not less than 150 international units litus or renal impairment or those also receiving potassium-spar- paired renal function found that guanfacine clearance and serum per mg and the potency of heparin sodium not intended for ing drugs such as ACE inhibitors, may present with symptoms of concentrations were not significantly different in the 2 groups, parenteral use is not less than 120 international units per mg, both hyperkalaemia. The UK CSM suggests2 that plasma-potassium suggesting that non-renal elimination plays an important role in calculated with reference to the dried substance. A white or al- concentration should be monitored in all patients with risk fac- patients with renal impairment. most white, hygroscopic powder. Freely soluble in water. A 1% tors, particularly those receiving heparin for more than 7 days. 1. Kirch W, et al. Elimination of guanfacine in patients with normal solution in water has a pH of 5.5 to 8.0. Store in airtight contain- The hyperkalaemia is usually transient or resolves when heparin and impaired renal function. Br J Clin Pharmacol 1980; 10 (sup- ers. is stopped and treatment is not generally required; fludrocorti- pl 1): 33S–35S. USP 31 (Heparin Sodium). The sodium salt of heparin with a sone was successfully used to treat resistant hyperkalaemia in a Uses and Administration potency, calculated on the dried basis, of not less than 140 USP patient in whom continued heparin therapy was necessary.3 units in each mg. USP heparin units are not equivalent to inter- Guanfacine is a centrally acting alpha2-adrenoceptor agonist Adrenal insufficiency secondary to adrenal haemorrhage has with actions and uses similar to those of clonidine (p.1248). It is national units. The source of the material is usually the intestinal also been associated with heparin; heparin-induced thrombocy- used in the management of hypertension (p.1171), although oth- mucosa or other suitable tissues of domestic mammals used for topenia may be implicated.4 food by man and should be stated on the label. A white or pale- er drugs are usually preferred. It may be used alone or with other 1. Oster JR, et al. Heparin-induced aldosterone suppression and hy- antihypertensives, particularly thiazide diuretics. It has also been coloured amorphous, odourless or almost odourless, hygroscop- perkalemia. Am J Med 1995; 98: 575–86. tried in the management of opioid withdrawal and in hyperactiv- ic powder. Soluble 1 in 20 of water. A 1% solution in water has 2. Committee on Safety of Medicines/Medicines Control Agency. ity disorders. a pH of 5.0 to 7.5. Store in airtight containers at temperatures be- Suppression of aldosterone secretion by heparin. Current Prob- low 40°, preferably between 15 and 30°. lems 1999; 25: 6. Also available at: Guanfacine is given orally as the hydrochloride, but doses are http://www.mhra.gov.uk/home/idcplg?IdcService=GET_ usually expressed in terms of the base. Guanfacine hydrochlo- Incompatibility. Incompatibility has been reported between FILE&dDocName=CON2023235&RevisionSelectionMethod= ride 1.15 mg is equivalent to about 1 mg of guanfacine. In hyper- heparin calcium or sodium and alteplase, amikacin sulfate, ami- LatestReleased (accessed 23/06/06) The symbol † denotes a preparation no longer actively marketed The symbol ⊗ denotes a substance whose use may be restricted in certain sports (see p.vii)